ArticleThe Journal of clinical investigation1998
Dominant-negative effect of a mutant cardiac troponin T on cardiac structure and function in transgenic mice.
Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 117 citations in OpenAlex.
- Obstructive hypertrophic cardiomyopathy: from genetic insights to a multimodal therapeutic approach with mavacamten, aficamten, and beyond.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- ESC working group on cardiac cellular electrophysiology position paper: relevance, opportunities, and limitations of experimental models for cardiac electrophysiology research.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2021Review
- Association Between Circulating Troponin Concentrations, Left Ventricular Systolic and Diastolic Functions, and Incident Heart Failure in Older Adults.JAMA cardiology · 2019Article
- INDUCED PLURIPOTENT STEM CELLS FOR MODELLING ENERGETIC ALTERATIONS IN HYPERTROPHIC CARDIOMYOPATHY.Conditioning medicine · 2019Article
- Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy.Circulation research · 2017Review
- Transgenic rabbit models for studying human cardiovascular diseases.Comparative medicine · 2012Review
- Myosin regulatory light chain mutation found in hypertrophic cardiomyopathy patients increases isometric force production in transgenic mice.The Biochemical journal · 2012Article
- Molecular biology of heart disease.World journal of cardiology · 2011Article
- Therapeutic potential of c-Myc inhibition in the treatment of hypertrophic cardiomyopathy.Therapeutic advances in chronic disease · 2011Article
- Differential interactions of thin filament proteins in two cardiac troponin T mouse models of hypertrophic and dilated cardiomyopathies.Cardiovascular research · 2008Article
- TGFbeta inducible early gene-1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathway.Journal of cellular biochemistry · 2007Article
- Antifibrotic effects of antioxidant N-acetylcysteine in a mouse model of human hypertrophic cardiomyopathy mutation.Journal of the American College of Cardiology · 2006Article
- Sarcomeric proteins and familial hypertrophic cardiomyopathy: linking mutations in structural proteins to complex cardiovascular phenotypes.Heart failure reviews · 2005Review
- Genetic causes of human heart failure.The Journal of clinical investigation · 2005Review
- Induction and reversal of cardiac phenotype of human hypertrophic cardiomyopathy mutation cardiac troponin T-Q92 in switch on-switch off bigenic mice.Journal of the American College of Cardiology · 2004Article
- Article
- Autopsy findings in siblings with hypertrophic cardiomyopathy caused by Arg92Trp mutation in the cardiac troponin T gene showing dilated cardiomyopathy-like features.Clinical cardiology · 2003Article
- The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model.The Journal of clinical investigation · 2002Article
- Molecular genetics and pathogenesis of hypertrophic cardiomyopathy.Minerva medica · 2001Review
- Disease-causing mutations in cardiac troponin T: identification of a critical tropomyosin-binding region.Biophysical journal · 2001Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hypertrophic cardiomyopathy (HCM) is a disease of sarcomeric proteins. The mechanism by which mutant sarcomeric proteins cause HCM is unknown. The leading hypothesis proposes that mutant sarcomeric proteins exert a dominant-negative effect on myocyte structure and function. To test this, we produced transgenic mice expressing low levels of normal or mutant human cardiac troponin T (cTnT). We constructed normal (cTnT-Arg92) and mutant (cTnT-Gln92) transgenes, driven by a murine cTnT promoter, and produced three normal and five mutant transgenic lines, which were identified by PCR and Southern blotting. Expression levels of the transgene proteins, detected using a specific antibody, ranged from 1 to 10% of the total cTnT pool. M-mode and Doppler echocardiography showed normal left ventricular dimensions and systolic function, but diastolic dysfunction in the mutant mice evidenced by a 50% reduction in the E/A ratio of mitral inflow velocities. Histological examination showed cardiac myocyte disarray in the mutant mice, which amounted to 1-15% of the total myocardium, and a twofold increase in the myocardial interstitial collagen content. Thus, the mutant cTnT-Gln92, responsible for human HCM, exerted a dominant-negative effect on cardiac structure and function leading to disarray, increased collagen synthesis, and diastolic dysfunction in transgenic mice.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.